Particulate hydroperoxidized poly-N-vinyl lactam, its preparation and use thereof

ABSTRACT

Particulate hydroperoxidized poly-N-vinyl lactam containing an average of about 0.5 to 20 hydroperoxy mole equivalents per mole of poly-N-vinyl lactam, the preparation of the same by subjecting particulate poly-N-vinyl lactam to an effective amount of ozone, and the use thereof in the preparation of graft copolymers possessing a low degree of extractibles, finding utility in a wide number of fields, particularly in biomedical devices, semipermeable membranes, and as films or fibers.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to particulate hydroperoxidizedpoly-N-vinyl lactam, a method of preparing the same, and the use thereofin the preparation of graft copolymers with at least one hydrophobicmonomer or hydrophilic monomer, and optionally a crosslinking agent. Theresulting copolymers possess unexpectedly low extractibles and goodmechanical properties and are useful in various biomedical applications,including contact lenses, medical surgical devices such as heart valves,vessel substitutes, mouth guards and denture liners, as semipermeablemembranes, and as films or fibers, e.g. for textile uses or as burn andwound dressings.

2. Prior Art

Polyvinyl pyrrolidone and its use in the preparation of graft or blockcopolymers with hydroxyethyl methacrylate finding applications for avariety of purposes, including contact lenses, is described in U.S. Pat.No. 3,621,079.

U.S. Pat. No. 3,639,524 discloses the graft or block copolymerization ofpolyvinyl pyrrolidone with N-vinyl pyrrolidone and a monomericmethacrylate, optionally in the presence of a crosslinking agent and acatalyst, to prepare a crosslinked xerogel which can be machined intocontact lens replicas and swollen in water to form a hydrated contactlens.

U.S. Pat. No. 3,894,129 discloses the graft or block copolymerization ofpolyvinyl lactams with a hydroxyalkyl methacrylate monomer in thepresence of a polymerization initiator at low temperatures andcontaining not more than 0.7% alkyl glycol dimethyacrylate crosslinker,followed by a post polymerization heat treatment in the manufacture ofcontact lenses. This patent stresses the exclusion of oxygen from thepolymerization reaction mixture on the grounds that oxygen inhibitspolymerization and can cause uneven degrees of polymerization andmonomer vaporization.

U.S. Pat. No. 4,138,408 discloses the graft or block copolymerization ofa polyvinyl lactam with a mixture of hydrophilic and hydrophobicpolymerizable monomers and a divinyl benzene or divinyltoluenecrosslinking agent in the manufacture of contact lenses.

Unfortunately, due to the incomplete incorporation of polyvinyl lactaminto the polymer network, such graft or block copolymers of the priorart, upon swelling with an aqueous medium, characteristically exhibit arelatively high degree of water soluble extractibles, comprisingpolyvinyl lactam containing residual products. Over a period of time,the mechanical properties of contact lenses made of such materials candegrade. Moreover, tinted lenses containing such extractibles can fadeover an extended period of time.

It is thus an object of the present invention to provide an improvedmodified poly-N-vinyl lactams of increased reactivity with hydrophobicand hydrophilic monomers, and copolymers resulting therefrom.

It is a further object of the invention to provide crosslinkedcopolymers with a significantly reduced degree of extractibles.

These and other objects of the invention are apparent from the followingdisclosures.

SUMMARY OF THE INVENTION

According to one aspect of the present invention, there is providedparticulate hydroperoxidized poly-N-vinyl lactam useful in thepreparation of graft or block copolymers with hydrophilic and/orhydrophobic monomers. A further aspect of the present invention relatesto copolymers prepared therefrom containing reduced water solubleextractibles as compared to non-hydroperoxidized poly-N-vinyl lactamderived copolymers. In a further aspect of the present invention thereis provided a method of preparing such hydroperoxidized poly-N-vinyllactams.

DETAILED DESCRIPTION OF THE INVENTION

One embodiment of the invention relates to a particulatehydroperoxidized derivative of a poly-N-vinyl lactam containing units ofthe formula ##STR1## wherein R is alkylene of 2 to 8 carbon atoms and nis between about 40 to about 4000, and mixtures thereof.

Generally, the polymers of formula I contain from 3 to 7 carbon atoms inthe heterocyclic ring thereof, including the carbonyl carbon atom, andpreferably contain from 4 to 6 such carbon atoms.

Some poly-N-vinyl lactams falling within the scope of formula I include,for example, poly-N-vinyl pyrrolidone, poly-N-vinyl-2-piperidone,poly-N-vinyl-2-caprolactam, poly-N-vinyl-3-methyl-2-caprolactam,poly-N-vinyl-3-methyl-2-piperidone, poly-N-vinyl-4-methyl2-piperidone,poly-N-vinyl-4-methyl-2-caprolactam, poly-N-vinyl-3-ethyl-2-pyrrolidone,poly-N-vinyl-4,5-dimethyl-2pyrrolidone, and the like.

Most preferred is polyvinylpyrrolidone.

The average value of n is preferably between about 50 and about 3600,most preferably between about 100 and about 800.

The starting material polymers according to formula I are known, per se,or can be prepared by methods well known in the art. For example, thecorresponding N-vinyl lactam can be polymerized under moderate toelevated temperatures e.g. between about 20° to 160° C., optionally inthe presence of a catalytic amount of a polymerization catalyst, such asazo-bis(isobutyronitrile), or a peroxide, such as hydrogen peroxide,di-tertiary butyl peroxide or t-butyl peroctoate, in the presence orabsence of an inert diluent, such as water, and optionally in thefurther presence of a base, such as ammonia or amine, to inhibithydrolysis and the like. As the artisan can appreciate, the reactionconditions can be adjusted to vary the degree of polymerization. Uponrecovery of the polymer, it can be dried if necessary and comminuted,for example, powdered.

The particle size of the poly-N-vinyl lactam can vary widely, butconveniently possesses a particle size between about 0.01 and about 200microns, preferably between about 0.1 and about 100 microns, and mostpreferably between about 0.5 and about 50 microns. Poly-N-vinyl lactamsare widely available commercially. For example, polyvinyl pyrrolidone isgenerally commerically available over a wide average molecular weightrange. Thus, the GAF Corporation supplies powdered polyvinyl pyrrolidonehaving an average molecular weight of about 10,000 (PVP K-15) to about360,000 (PVP K-90). A convenient polyvinyl pyrrolidone of GAFCorporation is Plasdone C Grade having a number molecular weight ofabout 37,000 and a molecular weight range of about 25,000-50,000. Alsoconvenient is PVP K-30, having an average molecular weight of about40,000, supplied by GAF Corporation.

The hydroperoxidized poly-N-vinyl lactam of the present inventiongenerally contains an average of between about 0.5 to about 20hydroperoxy (--OOH) mole equivalents per mole of poly-N-vinyl lactam.Preferably the polymer contains an average of between about 1 to about15 mole equivalents of hydroperoxy groups per mole of polymer, mostpreferably between about 1 to about 10 mole equivalent of hydroperoxygroups per mole of polymer.

In another embodiment of the invention, hydroperoxy groups can beconveniently introduced into the polymer by subjecting the particulatepolymer according to formula I to ozone (O₃), for example, by simplyintimately contacting the particulate polymer with an ozone containinggaseous carrier, such as ozonated air or ozonated oxygen, for a periodof time sufficient to result in the requisite uptake of ozone into thepolymer to form the desired hydroperoxidized polymer derivative. Thereaction temperature is generally not critical, and the reaction can beconducted over a wide temperature range, e.g. between 0° and 100° C.,preferably under ambient conditions.

In order to facilitate the reaction between the polymer and ozone toform the hydroperoxidized derivative, it may be desirable to insure thatthe ozonation is conducted in the presence of a small amount ofmoisture. Generally, the poly-N-vinyl lactam contains, under ambientconditions, sufficient adsorbed water, e.g. 5-9 weight percent in thecase of polyvinyl pyrrolidone, to facilitate the hydroperoxidation. Ifdesired, moisture can be added, for example by adjusting the humidity ormoisture content of the carrier gas to between about 20 and about 90percent of saturation.

Ordinarily ozone can conveniently be prepared in admixture with acarrier gas by passing an oxygen containing gas, such as air or oxygen,through a standard ozone generator. In the case of air, generally about2% ozone by weight is produced; the case of pure oxygen gas, about 4%ozone by weight is characteristically produced.

As stated above, moisture may be introduced into the reaction mixture bycontrolling the humidity of the ozone containing gas. However, attemptsto hydroperoxidize polyvinyl lactams in aqueous solutions are to beavoided, since under such conditions, the polyvinyl lactam ischaracteristically degraded into low molecular weight products,presumably due to chain scission.

The ozone containing gas may be contacted with the particulate polymeraccording to various methods, such as passing the gas over a shallowlayer of the particulates, or through a packed column containing thepolymer particulates, and preferably by passing the ozone containing gasthrough a fluidized bed of particulate polymer.

The resulting hydroperoxidized poly-N-vinyl lactam can be polymerizedwith at least one hydrophobic or hydrophilic monomer, or mixturesthereof, optionally in the presence of a crosslinking agent, to obtaingraft copolymers possessing unexpectedly low amounts of extractiblescoupled with good mechanical properties, and useful in a wide variety ofapplications, including contact lenses, medical surgical devices such asheart valves, vessel substitutes , mouth guards and dental liners,semipermeable membranes and films or fibers, e.g. for textile uses or asburn and wound dressings.

Suitable hydrophilic copolymerizable monomer include generally watersoluble conventional vinyl monomers such as:

acrylates and methacrylates of the general structure ##STR2## where R₂is hydrogen or methyl and R₃ is hydrogen or is an aliphatic hydrocarbongroup of up to about 10 carbon atoms substituted by one or more watersolubilizing groups such as carboxy, hydroxy, amino, loweralkylamino,di-loweralkylamino, a polyethyleneoxide group with from 2 to about 100repeating units, or substituted by one or more sulfate, phosphate,sulfonate, phosphonate, carboxamido, sulfonamido or phosphonamidogroups, or mixtures thereof;

acylamides and methacrylamides of the formula ##STR3## where R₂ and R₃are as defined above;

acylamides and methacrylamides of the formula ##STR4## where R₄ is loweralkyl of 1 to 3 carbon atoms and R₂ is as defined above;

maleates and fumarates of the formula

    R.sub.3 OOCCH═CHCOOR.sub.3

wherein R₃ is as defined above;

vinyl ethers of the formula

    H.sub.2 C═CH--O--R.sub.3

where R₃ is as defined above;

aliphatic vinyl compounds of the formula

    R.sub.2 CH═CHR.sub.3

where R₂ is as defined above and R₃ is as defined above with the provisothat R₃ is other than hydrogen; and vinyl substituted heterocycles, suchas vinyl pyridines, piperidines and imidazoles and N-vinyl lactams, suchas N-vinyl-2-pyrrolidone.

Included among the useful water soluble monomers are:

2-hydroxyethyl-; 2- and 3-hydroxypropyl-; 2,3-dihydroxypropyl-;polyethoxyethyl-; and polyethoxypropyl-acrylates, methacrylates,acrylamides and methacrylamides;

acrylamide, methacrylamide, N-methyl acrylamide, N-methylmethacrylamide, N,N-dimethylacrylamide, N,N-dimethyl methacrylamide;

N,N-dimethyl- and N,N-diethyl-aminoethyl acrylate and methacrylate andthe corresponding acrylamides and methacrylamides;

2- and 4-vinylpyridine; 4- and 2-methyl-5-vinylpyridine;N-methyl-4-vinylpiperidine; 2-methyl-1-vinylimidazole; N,N-dimethylallylamine; dimethylaminoethyl vinyl ether; N-vinylpyrrolidone;

acrylic and methacrylic acid; itaconic, crotonic, fumaric and maleicacids and the lower hydroxyalkyl monoand diesters thereof, such as the2-hydroxyethyl fumarate and maleate, sodium acrylate and methacrylate;maleic anhydride; 2-methacryloyloxyethylsulfonic acid and allylsulfonicacid.

Preferred water soluble monomers include 2-hydroxyethylmethacrylate,N,N-dimethylacrylamide, acrylic acid and methacrylic acid, and mostpreferably 2-hydroxyethylmethacrylate.

Suitable hydrophobic copolymerizable monomers include water insolubleconventional vinyl monomers such as:

acrylates and methacrylates of the general formula ##STR5## where R₂ isas defined above and R₅ is a straight chain or branched aliphatic,cycloaliphatic or aromatic group having up to 20 carbon atoms which isunsubstituted or substituted by one or more alkoxy, alkanoyloxy or alkylof up to 12 carbon atoms, or by halo, especially chloro or preferablyfluoro, or C₃ -C₅ polyalkyleneoxy of 2 to about 100 units;

acrylamides and methacylamides of the general formula ##STR6## where R₂and R₅ are defined above;

vinyl ethers of the formula

    H.sub.2 C═C--O--R.sub.5

where R₅ is as defined above;

vinyl esters of the formula

    H.sub.2 C═C--OCO--R.sub.5

where R₅ is as defined above;

maleates and fumarates of the formula

    R.sub.5 OOC--HC═CH--COOR.sub.5

where R₅ is as defined above;

and vinylic substituted hydrocarbons of the formula

    R.sub.2 CH═CHR.sub.5

where R₂ and R₅ are as defined above.

Useful hydrophobic monomers include, for example:

methyl, ethyl, propyl, isopropyl, butyl, ethoxyethyl, methoxyethyl,ethoxypropyl, phenyl, benzyl, cyclohexyl, hexafluoroisopropyl orn-octyl-acrylates and -methacrylates as well as the correspondingacrylamides and methacrylamides;

dimethylfumarate, dimethylmaleate, diethylfumarate, methyl vinyl ether,ethoxyethyl vinyl ether, vinyl acetate, vinyl propionate, vinylbenzoate, acrylonitrile, sytrene, alphamethyl styrene, 1-hexene, vinylchloride, vinyl methyl ketone, vinyl stearate, 2-hexene and 2-ethylhexylmethacrylate.

Generally, the copolymers are prepared by graft reacting a polymerizablemixture containing

(a) from about 1 to about 80 weight percent of the hydroperoxidizedpoly-N-vinyl lactam,

(b) optionally from about 0.1 to about 5 weight percent of acrosslinking agent, and

(c) from about 99 to about 20 weight percent of one or more hydrophilicor hydrophobic monomers or mixtures thereof. If desired the reactionmixture may contain a catalytic amount of a conventional catalystcharacteristically employed in polymerizing compounds having ethylenicunsaturation, and preferably a free radical catalyst. Of particularinterest are conventional peroxide and azo catalysts, such as hydrogenperoxide, benzoyl peroxide, tert.butyl peroctoate, benzoyl peroxide orazobis(isobutylnitrile). In many cases, an initiator is not needed, dueto the reactivity of the hydroperoxidized N-vinyl lactam. If desired orappropriate, the polymerization may be, at least in part, conducted inthe presence of actinic radiation or the like, with or without thepresence of a photoinitiator.

The graft polymerization can generally be carried out at temperaturesbetween about 20° to about 150° C., for a period between about 1 toabout 24 hours. It is understood that the time and temperature in such areaction are inversely related. Thus, temperatures employed in the upperend of the temperature range will generally provide reaction times nearthe lower end of the time range.

Depending upon the nature of the polymer mixture, it may be desirablefor the copolymers obtained from such polymerzations to be post cured,e.g. at a somewhat elevated temperature such as between about 60° C. toabout 150° C.

For the preparation of contact lenses, the polymer mixture may be castdirectly in the shape of the lens, or the polymerization may be carriedout in a mold having a shape convenient for further processing, such asin the shape of small cylinders or "buttons", which can then bemachined.

In a preferred embodiment of the invention, at least 50 weight percentof the monomer (c) component is a hydrophilic monomer, preferably a monoester of acrylic or methacylic acid and polyhydric alcohol, and mostpreferably hydroxyethyl methacrylate. Especially preferred arehydrophilic polymers capable of swelling in aqueous media to absorbbetween about 20% to about 80% water or other physiologically acceptableaqueous medium by weight, based upon the total hydrogel composition.

Suitable crosslinking agents are diolefinic monomers such as:

allyl acrylate and methacrylate; alkylene glycol and polyalkylene glycoldi-acrylates and -methacrylates, such as ethylene glycoldimethyacrylate, and propylene glycol dimethyacrylate; trimethylolpropane triacrylate; pentacrylthritol tetraacrylate, divinylbenzene;divinyl ether; divinyl sulfone;

bisphenol A diacrylate or methacrylate; methylene bisacrylamide; diallylphthalate; triallyl melamine; and hexamethylene acrylate andmethacrylate.

Of particular importance is the fact that the instant hydroperoxidizedpoly-N-vinyl lactam may be employed in conventional graft polymerizationprocesses to produce useful articles of commerce in substantially thesame manner as when employing poly-N-vinyl lactams, to obtain graftpolymers quite similar in appearance to conventional poly-N-vinyl lactamgraft polymers, but unexpectedly possessing unexpectedly lowextractibles.

Accordingly, the hydroperoxidized particulate poly-N-vinyl lactam of thepresent invention may advantageously be employed in the preparation ofgraft copolymers as described in U.S. Pat. Nos. 3,621,079; 3,700,761;4,123,407; and 4,123,408, for the uses described therein.

The following examples are presented for the purposes of illustrationonly and are not to be construed to limit the nature and scope of theinstant invention. All parts are by weight unless otherwise disclosed.

EXAMPLE 1

27 grams of poly-N-vinyl pyrrolidone, containing about 2 to 3 percent byweight absorbed water, having a weight average molecular weight of about40,000 (K-30 from GAF Corporation) and an average particle size of about5 microns is placed in a 100 ml cylindrical fluidized bed containing afrit on the botton through which ozonized oxygen gas, having aconcentration of 6% ozone, prepared by passing O₂ through an ozonegenerator, is passed upwardly through the particulate poly-N-vinylpyrrolidone at a rate of about 1 liter per minute gas for a period of 40minutes at a temperature of about 18° C. The resulting poly-N-vinylpyrrolidone is found to contain approximately 3 hydroperoxy moleequivalents per mole equivalent of poly-N-vinyl pyrrolidone.

EXAMPLE 2

As a comparative example, 18 grams of poly-N-vinyl pyrrolidone having aweight average molecular weight of about 40,000 (K-30 from GAFCorporation) is dissolved in about 204 grams of water, and ozonizedoxygen gas, having a concentration of 4% ozone is passed through thesolution at a rate of about 1 liter per minute of gas at a temperatureof about 18° C. After about 1 minute the solution turned clear anddegraded, as evidenced by a marked reduction in viscosity, illustratingscission of the poly-N-vinyl pyrrolidone under the reaction conditions.

EXAMPLE 3

2.0 grams of the peroxidized poly-N-vinyl pyrrolidone according toExample 1 is dissolved in a mixture of 9.3 grams hydroxyethylmethacrylate, 0.15 grams of ethyleneglycol dimethacrylate and 0.7 gramswater, the solution is mixed to insure uniformity, degassed by placingthe mixture in a vacuum, placed under a nitrogen blanket and subjectedto ultraviolet radiation under ambient room temperature conditions. Thesolution polymerized withing 30 minutes to afford a clear crosslinkedproduct suitable for use as a hydrophilic contact lens upon machiningthe product into a lens replica and swelling the machined lens replicawith water.

EXAMPLE 4

In a manner identical to Example 3, 2.0 grams of the peroxidizedpoly-N-vinyl pyrrolidone is dissolved in 9.3 grams hydroxyethylmethacrylate and 0.7 grams water and the solution polymerized within 30minutes to afford a clear polymerization product suitable for use as ahydrophilic contact lens material.

EXAMPLE 4

5.0 parts of ozonized poly-N-vinyl pyrrolidone prepared according toExample 1 is dissolved in a solution containing 19.5 partshydroxyethylmethacylate, 0.15 parts ethyleneglycol dimethacrylate, 0.05parts benzoin methyl ether, 0.3 parts methacrylic acid and 1.2 partswater, degassed by subjecting the mixture to a vaccum, placed under anitrogen blanket and poured into a contact lens replica mold. Thesolution in the mold is then subjected to ultraviolet radiation for twohours. The lens replica, upon equilibration with an isotonic salinesolution, contains about 55.6% water and possessing superior claritycoupled with good mechanical properties. Upon subjecting a dried lens toexhaustive soxhlet extraction with methanol, only a 4.6% total loss ofextractibles occurs. Similarly, upon subjecting a test lens prepared inaccordance with the above to boiling water for a period of three days,only about a 3% reduction in weight, on a dry basis, occurs.

EXAMPLE 6

In order to show the increased reactivity of the instant ozonatedpoly-N-vinyl pyrollidone as compared with unaltered poly-N-vinylpyrrolidone, two solutions are prepared. Solution A contains 2.0 gramsof ozonized poly-N-vinyl pyrrolidone prepared in accordance with Example1 dissolved in 8.0 grams hydroxyethyl methacrylate. Solution B contains2.0 grams of non-ozonized poly-N-vinyl pyrrolidone, identical to thestarting material of Example 1, dissolved in 8.0 grams of hydroxyethylmethacrylate. Both solutions are purged with nitrogen and subjected toultraviolet light under identical conditions. Within 15 minutes,solution A polymerized whereas no evident polymerization occurred withsolution B.

EXAMPLE 7

To further show the increased reactivity of the instant ozonizedpoly-N-vinyl pyrrolidone, solutions A and B were prepared according toExample 5. When solution A, containing 2.0 grams ozonated poly-N-vinylpyrrolidone dissolved in 8.0 grams hydroxymethyl methacrylate, is heatedto a temperature of 80° C. for a period of about 2 hours, the solutionpolymerizes into a hard polymeric mass. Solution B, containingnon-ozonated poly-N-vinyl pyrrolidone, but otherwise identical, does notpolymerize. This illustrates that ozonized poly-N-vinyl pyrrolidoneauto-initiates polymerization in the absence of added catalyst orultraviolet radiation.

What is claimed is:
 1. A particulate hydroperoxidized derivative of apoly-N-vinyl lactam containing units of the formula ##STR7## where R isalkylene of 2 to 8 carbon atoms, n is about 40 to about 4000, andwherein said derivative contains an average of between about 0.5 toabout 20 hydroperoxy equivalents per mole of poly-N-vinyl lactam; saidderivative being the result of the process comprising contacting aparticulate polymer having units of formula I with ozone.
 2. Aparticulate hydroperoxidized derivative according to claim 1, whereinsaid derivative possesses a particle size between about 0.01 and about200 microns.
 3. A particulate hydroperoxidized derivative according toclaim 2, possessing a particle size between about 0.1 and about 100microns.
 4. A particulate hydroperoxidized derivative according to claim1 wherein the average value of n is between about 50 and about
 3600. 5.A particulate hydroperoxidized derivative according to claim 1, whereinthe average value of n is between about 100 and about
 800. 6. Aparticulate hydroperoxidized derivative according to claim 1, containingan average of between about 1 and about 15 hydroperoxy equivalents permole of poly-N-vinyl lactam.